Mitohormesis and autophagic balance in Parkinson disease

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder worldwide, affecting 2% of the population over 65 years. This number will continue to rise as the life expectancy increases. Aging is the most important risk factor for developing PD; nevertheless the precise mechanisms leading to the clinical presence of the disease remain largely unknown. The fact that the age at onset of PD importantly modifies the natural history of the disease raises significant questions on the biological link between them. However, it must be acknowledged that 98% of the elderly population will not develop PD, thus suggesting the existence of some kind of ‘healthy aging’. Strikingly, for different reasons, aging is a variable rarely incorporated in most of experimental approaches in the study of PD [1]. Considering the definition of aging as “a persistent decline in the age-specific fitness components of an organism due to internal physiological degeneration” [2] the fact that the degeneration process is not the same for all tissues within the same organism, and consequently not for all individuals, is critical when developing experimental models directed to the study of neurodegenerative diseases. Additionally, the recent recognition that PD is not a disease constrained to the loss of dopaminergic neurons in the substantia nigra, but a complex series of events that lead to a common clinical outcome, has greatly increased the potential areas of investigation directed towards the establishment of novel experimental models, biomarkers and disease-modifying therapies [3]. In this sense, the use of patient’s derived cell models for research preserving aging-related variables of patients and individual genetic and some epigenetics’ characteristics is gaining relevance. While most of PD cases are idiopathic, monogenic forms of the disease are demonstrated in 5-10% of the cases. The study of the genes responsible for these monogenic forms of the disease has proven to be of great utility to further dissect the pathogenic mechanisms and metabolic pathways that lead to PD. Interestingly, the role of mitochondrial function (responsible of energy supply and oxidative stress generation) and autophagy (aimed to remove and recycle damaged cell components) are being tested in these patients and these models as a trigger or a protective factor for the development of both aging and PD. Editorial